Abstract
Objective This study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking. Methods The main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of “drugs-active components-disease targets” was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software. Results Seventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities. Conclusion Modified Danggui Sini Decoction has the hierarchical network characteristics of “multicomponent, multitarget, multifunction, and multipathway” in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.
Highlights
Knee osteoarthritis (KOA) is a common degenerative bone and joint disease, which is caused by the imbalance of degradation synthesis coupling of chondrocytes, extracellular matrix, and subchondral bone under the action of mechanical and biological factors [1]
Choose TCMSP Database [5], with the oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18 as the screening conditions [6, 7], the constituent herbs of Modified Danggui Sini Decoction were searched in turn, and the main chemical components of the prescription were obtained after supplementing the common components recorded in Chinese Pharmacopoeia [8]
Main Components of Modified Danggui Sini Decoction and Treatment Targets of KOA. rough TCMSP database, the constituent herbs of Modified Danggui Sini Decoction were searched in turn
Summary
Knee osteoarthritis (KOA) is a common degenerative bone and joint disease, which is caused by the imbalance of degradation synthesis coupling of chondrocytes, extracellular matrix, and subchondral bone under the action of mechanical and biological factors [1]. Modified Danggui Sini Decoction is a classic prescription of Traditional Chinese Medicine (TCM) in treating KOA. It is composed of Danggui nourishing blood and Guizhi warming meridians, which is combined as the monarch medicine. Evidence-Based Complementary and Alternative Medicine and harmonize nutrient, and Xixin helps Guizhi to warm and dredge blood vessels. It is supplemented with Tongcao, Niuxi, and Duzhong to invigorate kidney and bone, leading meridians to the affected areas. Combined with GO function analysis, KEGG pathway enrichment analysis, and molecular docking technology, the mechanism and scientific connotation of Modified Danggui Sini Decoction in the treatment of KOA were revealed, providing an objective experimental basis for clinical application of TCM treatment of KOA, and providing new ideas and methods for the treatment of orthopedic and traumatology related diseases guided by TCM theory
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